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?????? Lymphokine

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Title: ?????? Lymphokine


1
?????? Lymphokine ???
??????????? ?????? ????
404741028 ??????? ?????????????
?????????????????
2
Adoptive Cellular Immunotherapy
?????????????????????????????????????????????????
??????????????????????????????????????????????????
????? ????????????? ????????????????????? 2
?????? 1. Lymphokine-Activated Killer (LAK) Cell
Therapy ?????????????????? LAK cells ???????????
??????????????????????????????????????????????????
?????????????????? IL-2 ???????????
???????????????????????????????????????? NK cell
??????????????????????????????????????????????????
???????????????????????????????????
???????????????????????????? 2.
Tumor-infilirating lymphocytes therapy ???????
Mononuclear cells ??????? ????????????????????????
?????????????????? LAK cells??????????????????????
???????????????????????? TILs ???????????? NK ???
CTLs ???????????????????????????
?????????????????? IL-2 ??????????????????????????
?????????????????????



3
Cytokine Therapy ??????????????? cytokine
??????????????????????????????????????????????????
?????????????????? ?????? cytokine
??????????????????????????????????????????????????
?????????????????????????????? cytokine
?????????????????????????????? 1. Interleukin-2
(IL-2) ??????????????? ?????????????? Adoptive
Cellular jImmunotherapy ????????????? 20-40
??????????????? Melanoma ?????????????? IL-2
??????????? NK cells ???/???? CTLs????????? LAK
cell ??????????????????????????????? ??????
???????????? ?????????????? IL-2 ?????????????
Lymphocytes ??????????????????? TNF, IFN-a ???
Lymphotoxin ????????????????????????? IL-4
????????????????? CTLs ???????????????????????????
???????????? 2. TNF ?????????????????????????????
?????????????? ???????????????????????????????????
??????????????????????????????????
4
3. Alpha-interferon (IFN-a) ???????? TYPEI
Interferon ????????????????????
???????????????????????????????????????????
expression ??? class I MHC ???????????????????????
??????????????????? ????? 10-15 ??????????,
Melanona, Kaposi sarcoma ????? 45-50
????????????????????? ????? 80-90 ?? Hairy cell
leukemia 4. IFN-beta ????????????????????????????
???????????????????????????????????? ??????
IFN-beta ??????????????????????? NK cell ???
Macrophage 5. Hematopoietic growth factors
????????????? GM-CSF (Granulocyte-Macrophage
Colony Stimulating Factor) ??? G-CSF (Granulocyte
colony stimulating Factor) ???????????????????????
????????????????????????????????????
?????????????????????????? ????????????????????
Transfect ?????????????????????????? Cytokine
Genes ????????????????????????????????????????????
???? ??????????????? cytokine ????????????????????
?????????????????????????????????????? cytokine
gene ????????????????????????? IL-2, IL-4 ???
IFN-a genes ?????????????????????????????????
5
???????????????????????????? (Host defense
mechanism) ????????????????????????
??????????????? (The immune system) ??????????
???????????? (Immunology) ????????????????????????
???????????????????? ????????????????????????
(immune response) ???????????????????????????
????????????????????????????????????
?????????????????????????????????????????? 419424
???????? (antigen, Ag) ??????????????????? 1.
???????????? ?????????????????????????????????????
? (immunogenicity) ???????????? immunogen 2.
??????????????????????????????????????????????????
? ???????????????? antibody ???? T-lymphocyte
????????????? antigenicity
6
?????????????????????????????? 1. ??????????????
(foreigness) 2. ?????????????????
????????????????????????????????????????
?????????????? ????????????????? ????????????????
?????????????????????????????????????? ??????
????????????? ????????????? ?????
???????????????? ???????? 3. ?????? (size)
?????????????? ???????????????????????????????????
????????????? ????????????????????????????????
???????? Hapten ??????? immunogen
??????????????????????????????? carrier protein
?????????????????????? ANTIGENIC DETERMINANTS
(EPITOPE)????????????????????????????????????????
????????????????????????????????? T- lymphocyte
???????????????????????? ?????????????????????????
????????????????????????????? ????????????????? 1
??????????? antigenic determinant ??????
7
?????????????????????? ???????????????????????????
?????????????????????????????????????????????
pluripotential stem cells ????????????????????????
????????????????? 3 ?????? 1. lymphoid lineage
2. myeloid lineage 3. Third population cells
lymphoid lineage ??????????? lymphocyte
?????????????????? T-lymphocyte ??? B-lymphocyte
myeloid lineage ??????????? PMN
(polymorphonuclear cells) , monocyte ???
macrophage Third population cells ???????????
natural killer cell (NK cell) ??? Killer cell (K
cell) RETICULO ENDOTHELIAL SYSTEM (RE
SYSTEM) ???????????? (network) ???????????????????
???????????????????? (phagocytosis)
??????????????????? ?????? ????? ??? ???? ??
???????? ????????????? ??? ???? ????????? .
8
THE LYMPHOID SYSTEM ????????????? ??????????
lymphocyte, endothelial cells ????????????????????
????? ???? ????????? ???????????????????????? 1.
primary lymphoid organs ??????????????????????????
?????????? ??? ???????? ??? ????????? 2.
secondary lymphoid organs ??????????????????
lymphocyte ??????????????? ??????????????????????
?????????? ???????????????????????? (payer's
patch) ???? ??????????????????????????????
(???????????????) ?? 2 ??? ??? 1.
?????????????????????????????? (non specific
immune response ???? natural immunity) 2.
??????????????????????????? (specific immune
response ???? acquired immunity).
9
??????????????????????????? (non specific immune
response, natural resistance, innate
immunnity???? natural immunity) 1.
?????????????????????? (barrier) ???????????
?????????? ?????? (cilia) ????????? lysozyme
??????? ?????? ?????? ?????? ?????????????????
spermine ?????????? ????? ?????? 2. ?????????
(inflammatory response) ??????????????????????????
?????? ??? ???? ??? ??????????????????????????????
?????????????????? phagocyte ?????????????????????
?????? neutrophil macrophage ??? monocyte
????????????????????????????????? ????
??????????????????????????? 3.
??????????????????? (normal flora) ??????????????
vagina 4. Natural Killer (NK) cell
????????????????????? ????????????? 5.
????????????? ???? interferon (IFN), complement
(C), C-reactive protein .
10
???????????????????????? (specific immune
response ???? acquired immunity) ?????????????????
?????????????????????????????? lymphocyte
???????????????????????? ????????????????? 1.
Humoral immunity ???????? B-lymphocyte ??? 2.
Cell mediated immunity ???????? T-lymphocyte
11
HUMORAL IMMUNITY (HI, HMI) ???????????????????????
????????????????????????????? ?????????
(antibody, Ab) ???????????????????????????????????
? Antibody ??????????? antiserum, immunoglobulin
(Ig) ???????????????????????? glycoprotein
??????????????????????????? gamma globulin
????????????????????????????????????????? (Y)
?????????????????????? 4 ???? ????????????????????
????? heavy chain (H chain) ??????????????????????
???????? light chain (L chain) ???????????????????
?? disulfide bond (-s-s-) ????????????????????????
???? 4 ???? (class) ?????????? H-chain ??? IgG,
IgA, IgM, IgD, IgE IgM ??????????????????????????
??? class ???? ?????????? ???????????? IgG
???????????????? ????????? IgA
??????????????????? ????? ?????
???????????????????? IgE ????????????????????????
?????????????????????????? IgD ???????????
B-lymphocyte ??????????????????????????? (antigen
receptor) .
12
Tumor antigens ???????????????????????????????????
???? Humoral ??? cell mediated ???????????????????
????????????? ????????????????????????????????????
????????????? 1. ???????? antibody ???????
???????????? Ab ?????????? tumor antigens ????
Tla Ag ??????????????????????????????
????????????? Ab ??? EBV-coded antigens
???????????????????????? (lymphoma)???????????????
?????????Ab???????????????????????????????????????
??????????? ???????????????? antibody
???????????????????????????? Antibody dependent
cell mediated cytotoxicity (ADCC) ??? Macrophage
???? NK cells 2. Cytolytic T-lymphocytes (CTLs)
??????????????????????????????????????????????????
?????????? ???????????????????????? CTLs
??????????????????????? Class I MHC restricted
13
3. Natural Killer cells (N cells) NK cell
??????????????????????????????????????????????????
????? CTLs ????????????????????????? MHC
????????????????NK????????????????????????????????
????????????? ???????????????????????? Ab
?????????????????? Fc-receptor ????????? NK
???????????????? NK cell ?????????????????????????
?????????????????? Interferons, Tumor Necrosis
Factor (TNF) ??? Interleukin-2 (IL-2) ???????
??????????? NK ????????????????????????? T-cells
??? Macrophage ????????????????? cytokines
????????????? ??????????????????????????????
Lymphokine activated killer (LAK) cells
????????????????????????????????????????? NK cell
?????????????????????????????????????????
4. Macrophages ???????????????????????????
??????????????? macrophages ?? Fc receptor
???????????? NK cell ????????????????????????????
Ab ????????????? ?????????????????????????????????
????????????????????? ????????????? Lysosomal
Enzymes ??? Reactive Oxygen Metabolites ???????
Nitric oxide Activated macrophages ???????????
TNF ??????????????????????????????????????????????
?????? TNF ???????????????????????????????? . .
14
CELL MEDIATED IMMUNITY (CMI) ?????????????????????
????????? T-lymphocyte ???????????????????????????
???? ????????????????????????????? lymphokine
????????????????? macrophage ?????????????????????
???????????????? ??????????? CMI ??? 1.
???????????????????? (delayed type
hypersensitivity) ??????????? tuberculin test
??????????????????????????????? 2.
????????????????????????? (graft rejection) 3.
??????????????????? .
15
??????? T-lymphocyte T-helper (
Th)?????????????????????????????????????
????????????????????????????????????????
T-suppressor (Ts)?????????????????????????? T
??? B-lymphocytes T-cytotoxic (Tc)???????????????
???????????????????????????????? T-effector ????
T-delayed type hypersensitivity (Tdth)
?????????????????????? lymphokine ??????????????
?????????????? (delayed type hypersensitivity)
???????????????? cell mediate immunity
16
??????????????????????????????????? (CMI) 1.
lymphokines ???? chemotactic factor
??????????????????? phagocyte ????????????????????
???? ???????????????????????????????????? 2..
lymphokines ???? macrophage activating factor
??????? macrophage ????????? ???????????????? 3.
T-cytotoxic (Tc) ????????????????????????????????
????????????????? 4. ?????? ?????????????????????
???? ??? Ts ??? Th 5. lymphokine ???? migration
inhibition factor ??????????? macrophage
????????????????????????????????????.
17
???????????????? (The complement
system) ?????????????????????????????????????????
???????????????????? ?????????????????????????????
???? ?????????????????????????????????????????????
?????????? ???????????? complement component
???????????????????????? ??????????????????????
(activate) ?????????????? complement ?????????
1. ????????????????????????????????? (cell
lysis) 2. complement component ?????? ???? C3a
C5a ???????????????? macrophage
?????????????????????????? 3. ???????????????????
???????????? 4. complement component ?????? ????
C4b ???? opsonin ???????????????? ?????
macrophage ????????????????????????? .
18
???????????????????? 1. opsonization
????????????????????????????????????
???????????????????????????? (phagocytosis)
??????????????????? 2. antitoxicity
??????????????????????? (toxin) 3. ???????
complement ??????????????? ???????????????????????
??????? (cell lysis) 4. Neutralization
?????????????????????? ???????????????????????
?????????
19
Lymphokine Soluble cytokines secreted by
lymphocytes , which have a variety of effects on
lymphocytes and other cell types. Cytokine
Cytokines are soluble glycoproteins released by
cells of the immune system , which act
nonenzymatically through specific receptors to
regulate immune responses. Cytokines resemble
hormones in that they act at low concentrations
bound with high affinity to a specific receptor .

20
Lymphocyte A white blood cell of the mononuclear
leukocyte subgroup (like macrophage / monocytes
). Lymphocytes identify foreign substances and
germs (bacteria or viruses) in the body and
produce antibodies and cells that specifically
target them. It takes from several days to weeks
for lymphocytes to recognize and attack a new
foreign substance. The main lymphocyte
sub-types are B-Cells . Special B cells
produce specific antibodies, proteins that help
destroy foreign substances. T-Cells . T-cells
attack virus-infected cells, foreign tissue, and
cancer cells. They also produce a number of
substances that regulate the immune response.
21
NK Cells . Among other functions, natural
killer cells destroy cancer cells and
virus-infected cells through phagocytosis and by
producing substances that can kill such cells.
Null cells . An early population of lymphocytes
bearing neither T-cell nor B-cell differentiation
antigens. Lymphocytes are small cells with
virtually no cytoplasm, found in the blood, in
all tissue and in lymphoid organs, such as lymph
nodes , the tonsils , thymus gland , spleen .
22
lymphokine - a cytokine secreted by helper T
cells in response to stimulation by antigens and
that play a role in cell-mediated immunity
cytokine - any of various proteins secreted by
cells of the immune system that serve to regulate
the immune system interleukin - any of several
lymphokines that promote macrophages and killer T
cells and B cells and other components of the
immune system.
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